Título:
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Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program
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Autor/a:
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Stanzani, Elisabetta; Martínez Soler, Fina; Martín Mateos, Teresa; Vidal, Noemí; Villanueva Garatachea, Alberto; Pujana Genestar, M. Ángel; Serra-Musach, Jordi; Iglesia, Núria de la; Giménez Bonafé, Pepita; Tortosa i Moreno, Avelina
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Otros autores:
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Universitat de Barcelona |
Abstract:
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Glioblastoma (GBM) still remains an incurable disease being radiotherapy (RT) the mainstay treatment. Glioblastoma intra-tumoral heterogeneity and GlioblastomaInitiating Cells (GICs) challenge the design of effective therapies. We investigated GICs and non-GICs response to RT in a paired in-vitro model and addressed molecular programs activated in GICs after RT. Established GICs heterogeneously expressed several GICs markers and displayed a mesenchymal signature. Upon fractionated RT, GICs reported higher radioresistance compared to non-GICs and showed lower α- and β-values, according to the Linear Quadratic Model interpretation of the survival curves. Moreover, a significant correlation was observed between GICs radiosensitivity and patient disease-free survival. Transcriptome analysis of GICs after acquisition of a radioresistant phenotype reported significant activation of Proneural-to-Mesenchymal transition (PMT) and pro-inflammatory pathways, being STAT3 and IL6 the major players. Our findings support a leading role of mesenchymal GICs in defining patient response to RT and provide the grounds for targeted therapies based on the blockade of inflammatory pathways to overcome GBM radioresistance. |
Materia(s):
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-Glioma -Tumors cerebrals -Cèl·lules mare -Resistència als medicaments -Radioteràpia -Gliomas -Brain tumors -Stem cells -Drug resistance -Radiotherapy |
Derechos:
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cc-by (c) Stanzani, Elisabetta et al., 2017
http://creativecommons.org/licenses/by/3.0/es |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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Impact Journals
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